A combined ultrastructural, cytochemical and physiological analysis of protein transport and membrane circulation in two nerve tissue culture model systems; chick sympathetic neurons and fetal mouse spinal cord neurons. In neurons many proteins made in perikarya are transported down axons either by microtubule related processes or within the cisternae of axonal smooth endoplasmic reticulum. Associated with this transport of protein is a circulation or flow of membrane down the axon where it may be used in the formation of structures such as synaptic vesicles. At synaptic terminals the membrane-delimited synaptic vesicles are utilized for neurotransmission by exocytosis. The membrane that is added to the presynaptic surface during exocytosis is retrieved by endocytosis in the form of small vesicles that may be reused for transmitter release or turned over and removed from the terminals. Transport of membrane and protein from terminals by retrograde flow leads to accumulations in various perikaryal bodies such as lysosomes that are involved in intracellular digestive processes. The present studies are aimed at determining what specific proteins such as dopamine-B-hydroxylase are transported within the axonal reticulum elucidating the structure of the axonal reticulum to better understand the mechanism of axonal transport by this route, to determine the means by which anteriorgrade and retrograde transported may be segregated from each other within the reticulum, to evaluate the role of retrograde transport in the turnover of synaptic vesicle membrane, and begin to study the energy mediated regulation of retrograde axonal transport.